Occlusion of the upper airway during sleep is the essential event of obstructive sleep apnea (OSA). Diminished activity of upper airway muscles during sleep as well as relatively smaller and more compliant airways during wakefulness have been found in patients with OSA. Of the many muscles of the upper airway, the tongue (genioglossus) plays an especially important role in the pathogenesis of OSA because it forms the anterior border of the narrowest part of the upper airway, the oropharynx. Hence, activation of the genioglossus that is insufficient to resist the negative pharyngeal pressure generated by inspiratory muscles may allow the tongue to lapse backward and occlude the airway. To date, electrical activity of the genioglossus and upper airway mechanics have been studied in separate experiments, but the relationships between genioglossal activity and a physiologically relevant mechanical effect of genioglossal activity, pharyngeal resistance, has not been studied. The study of this relationship in normal subjects and patients with OSA is the aim of the first studies I have proposed. Subsequent studies are designed to investigate in awake humans the role of reflex mechanisms controlling upper airway muscle activity that have been described only in anesthetized animals. The relevance of these reflexes in normal upper airway control is tested in the next study, which looks at the effect of changing nasal resistance on pharyngeal resistance and genioglossal electromyographic (EMG) activity: I suspect that changing nasal resistance will stimulate reflex mechanisms enhancing upper airway muscle activity. Using quantitative data on the neuromechanical coupling between genioglossal EMG activity and upper airway mechanics derived from the experiments above, I plan to develop a computer model of the upper airway to test the effect of alterations in airway function that are allegedly important in the pathogenesis of OSA. Finally, if diminished genioglossal activity is important in the pathogenesis of OSA, then external stimulation of the tongue might prevent airway occlusion. We have already developed a noninvasive surface EMG electrode for the tongue that I hope to develop as a genioglossal stimulating electrode for therapeutic use.